J. R. W. Harris

Changing disease patterns in patients with AIDS in a referral centre in the United Kingdom: the changing face of AIDS.

OBJECTIVE--To study the changes in morbidity, mortality, and survival patterns in a population of patients with AIDS in the United Kingdom from 1982 to 1989. DESIGN--A retrospective analysis of inpatient and outpatient records of patients with AIDS. SUBJECTS--347 Patients with AIDS, predominantly homosexual or bisexual men. SETTING--Departments of immunology and genitourinary medicine, St Marys Hospital, London. MAIN OUTCOME MEASURES--Presenting diagnosis of AIDS, occurrence of other opportunist diseases, cause of death, and survival since AIDS was diagnosed, in particular for those patients with Pneumocystis carinii pneumonia or Kaposis sarcoma. RESULTS--The overall proportion of patients who developed P carinii pneumonia dropped from 56% (20/36) in 1984 to 24% (46/194) in 1989, although it has remained the index diagnosis in about half of new patients. Kaposis sarcoma has decreased as index diagnosis from 30% (20/67) to 20% (15/74) over the same period, though the prevalence has remained constant at around 35%. P carinii pneumonia accounted for 46% (16/35) of known causes of death in 1986 but only 3% (1/31) in 1989. Conversely, deaths due to Kaposis sarcoma rose from 14% (1/7) to 32% (10/31) between 1984 and 1989. Lymphoma accounted for an increased proportion of deaths among these patients with 16% (5/31) of deaths in 1989. Their median survival increased from 10 months in 1984-6 to 20 months in 1987. CONCLUSIONS--The changing patterns of disease in patients with AIDS have important implications both for health care provision and future medical research. Medical and nursing provision must be made for the increased morbidity of these diseases and the increased survival of these patients. Research should now be directed towards developing effective treatments for the opportunist infections which are currently more difficult to treat, the secondary malignancies of AIDS, as well as more effective immunorestorative treatments. Future changes in disease patterns must be recognised at an early stage so that resources can be adequately planned and allocated.

Liposomal doxorubicin (doxil): an effective new treatment for Kaposi's sarcoma in AIDS

The objective of this study was to assess the efficacy and toxicity of a novel Stealth liposomal encapsulated formulation of doxorubicin (Doxil). A Phase I/II dose escalation study was carried out in a specialist HIV oncology unit in a teaching hospital (predominantly in an outpatient department). Fifteen patients with HIV related, biopsy confirmed, cutaneous Kaposis sarcoma, with or without visceral involvement of sufficient severity to require systemic chemotherapy, were treated. Most patients had poor prognosis disease as assessed by the Tumour/Immune status/Systemic symptoms (TIS) system and Karnofsky indices; six patients had previously received combination chemotherapy. Primary treatment consisted of a dose of Doxil 10 mg/m2, repeated after 2 weeks. If the Kaposis sarcoma (KS) responded and the treatment was tolerated, the patient began maintenance therapy at the same dose every 2 weeks. If there was no clinical response, the dose was increased to 20 mg/m2 for the further two cycles, before proceeding to maintenance therapy. Treatment continued until other intercurrent disease, lack of further response, patient preference, or toxicity precluded further treatment. Tumour response was assessed 2 weeks after completion of at least two cycles of chemotherapy. Toxicity was assessed for each cycle. Doxil was well tolerated, and toxicity was manageable, the principal toxicity being haematological. A partial response rate of 11/15 (73%) was achieved, with disease stabilization in the remaining patients. We conclude that Doxil is an effective palliative treatment for epidemic KS in a patient group with a poor predicted outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

THREE-YEAR PROSPECTIVE STUDY OF HTLV-III/LAV INFECTION IN HOMOSEXUAL MEN

170 symptom-free homosexual men were recruited in London in 1982-83 and 133 were evaluable in 1983-85. Of the 33 who were seropositive to HTLV-III/LAV at entry, 4 (12%) progressed to AIDS, 16 (48%) progressed to persistent generalised lymphadenopathy (PGL), and 13 (40%) remained symptom-free. A further 15 men seroconverted during the study (7% per annum), of whom 8 progressed to PGL. Serial estimations of T lymphocyte subsets showed progressive reduction in T4 numbers in the seropositive groups, but these indices also varied widely in the seronegative group. Counts of T4 and T8 cells or T4/T8 ratio at entry were not of prognostic value. Seronegative subjects were as likely as seropositives to have abnormal immunological tests. Serial measurement of T lymphocyte subsets seems to be of little prognostic or clinical value in the monitoring of populations infected with the HTLV-III/LAV virus. The strongest association with prognosis was an episode of sexually transmitted disease in the six months before entry to the study. This supports the hypothesis that intercurrent infection may be an important co-factor in the acquisition of HTLV-III/LAV infection, and in subsequent disease progression.

Pneumothorax in patients with AIDS

Eighty-seven inpatients were treated for 93 episodes of Pneumocystis carinii at St Marys Hospital between January 1989 and December 1990. During this period, 298 patients with the acquired immunodeficiency syndrome (AIDS) were treated at this hospital. Sixteen episodes of pneumothorax occurred and 12 of these, occurring in ten patients, were unrelated to procedure. In six of 12 (50%), the pneumothoraces occurred concurrently with Pneumocystis carinii pneumonia (PCP) and in ten (83%) cases there was a past history of PCP. Bilateral pneumothorax occurred in five cases (42%). In seven (58%) of the cases, patients had been using aerosolized pentamidine as prophylaxis for PCP. This retrospective study confirms the association of pneumothorax with current PCP and also shows an association with previous infection. The use of aerosolized pentamidine was not associated with pneumothorax development. It is important to suspect pneumothorax in a patient with PCP who deteriorates acutely. The high incidence of bilateral pneumothorax means that pleurodesis should be considered early.

Inflammatory joint disease and human immunodeficiency virus infection

Nine men positive for antibody to human immunodeficiency virus (HIV) who developed peripheral, non-erosive arthritis were followed up. The clinical features were compatible with reactive arthritis but were atypical in several respects: the joint symptoms were generally severe, persistent, and unresponsive to non-steroidal anti-inflammatory drugs. The onset of arthritis was associated with various infections, none of which are known to be associated with the development of reactive arthritis. HLA typing was performed for three patients, all of whom were positive for HLA-B27. HIV was isolated from the synovial fluid of one patient. No patient had AIDS before developing arthritis, but four progressed to having AIDS after a mean of 7·5 months, and two died. Arthritis resolved in only one patient. The possibility of HIV infection should be considered in all patients with conditions suggesting reactive arthritis. Synovitis in patients with severe immunodeficiency has important pathogenetic implications.

Penile dermatoses : a clinical and histopathological study

OBJECTIVE--To assess the spectrum of genital dermatological conditions affecting men and compare the clinical and histopathological diagnoses. DESIGN--Prospective study over a one year period. SETTING--A central London teaching hospital. PATIENTS--Seventy one patients with unresponsive penile dermatoses attending a specific internal referral clinic within the department of genitourinary medicine and 36 patients undergoing penile biopsy following attendance at other departments within the same hospital. METHODS--Full dermatological assessment of patients attending the specific clinic. Standard histopathological methods were used in the diagnosis of biopsy specimens. OUTCOME MEASURED--Clinico-pathological diagnosis of cutaneous penile abnormalities. RESULTS--Description of the range and relative frequency of penile dermatological conditions. The most common histopathological diagnosis was of non specific dermatitis. Twenty seven percent (16 of 61) of patients attending the specific clinic and 33% (12 of 36) of men attending other departments had conditions requiring long term follow up. CONCLUSIONS--The ranges of penile dermatoses presenting to the different departments were broadly similar. Penile biopsy was shown to be a safe and clinically informative procedure. In the genitourinary clinic setting, clinical diagnosis prior to biopsy was found frequently to be inaccurate.

Mycobacterium malmoense infection in HIV positive patients

Mycobacterium malmoense is a non-tuberculous mycobacterium which has previously been associated with underlying pulmonary pathology and depressed immunity. We describe two patients infected with human immunodeficiency virus from whom M. malmoense was isolated, and discuss its treatment and possible pathogenic role.

Factors affecting seropositivity to human T cell lymphotropic virus type III (HTLV-III) or lymphadenopathy associated virus (LAV) and progression of disease in sexual partners of patients with AIDS.

Fifty four sexual partners of homosexual men with the acquired immune deficiency syndrome (AIDS) were studied, of whom 32 were seropositive and 22 seronegative for human T cell lymphotropic virus type III or lymphadenopathy virus (HTLV-III/LAV) antibody, which showed that repeated exposure by anal intercourse does not necessarily lead to seroconversion. Seropositivity to HTLV-III/LAV was not associated with the absolute number of sexual partners, receptive anal intercourse, or the use of recreational drugs, but was associated with a history of other sexually transmitted diseases (STDs), particularly in the year preceding the patients initial examination. Acquisition of an STD after the date of last sexual contact with a person with AIDS was strongly associated (p less than 0.001) with the development of persistent generalised lymphadenopathy (PGL). Concurrent or recent STDs would seem to be an important cofactor in developing antibody to HTLV-III/LAV and in the progression of infection from a person being asymptomatic to having PGL.

Campylobacter pylori in the upper gastrointestinal tract of patients with HIV-1 infection.

Fifty one patients with human immuno-deficiency virus (HIV-1) infection who had been consecutively endoscoped for upper gastrointestinal symptoms were biopsied (stomach or duodenum, or both) and compared with 59 age and sex matched controls for the presence of Campylobacter pylori. In 28 (47%) of the control group but in only seven (14%) of the HIV seropositive patients were C pylori seen on histological examination (p less than 0.001, odds ratio 5.6, 95% confidence interval 2.2-14.5). Sixteen patients who were HIV antibody positive had other index diseases for the diagnosis of AIDS in the biopsy material and, when these were excluded, comparison with the control group still showed a significant difference; p less than 0.01, odds ratio 3.6, 95%, confidence interval 1.4-9.6. In this series, therefore, C pylori were far less common in HIV antibody positive patients than in controls. Among the HIV positive patients, a higher proportion of C pylori negative cases had AIDS but this trend was not significant. The findings of this study indicate that whatever abnormalities of cell mediated mucosal immunoregulation are caused by HIV infection, they do not seem to be important in the response to infection by C pylori.

Microbiological survey of acute epididymitis.

In an 18 month period, 198 men presented with a painful, swollen, and tender epididymis or testicular or scrotal pain. Fifty were excluded from analysis because of prior antibiotic treatment or a history of the disease, or both. Of the remaining patients, epididymitis was not diagnosed in 108, though 23 (21%) of them had urethritis. Thus 40 men were seen who had acute unilateral epididymitis. Of the 27 less than 35 years old, 13 (48%) had a urethral chlamydial infection and two others a gonococcal infection. Sexually transmitted micro-organisms were not confined, however, to the younger age group, though only two (15%) of 13 men who were 35 years or older had a urethral chlamydial infection. Most, that is 29 (73%), of the patients with acute epididymitis also had urethritis when first seen. Urethral micro-organisms were found most often in 13 men who had severe epididymitis, chlamydial infection occurring in eight (62%) of the patients in this category.